Stabilized vitamin C formulations

ABSTRACT

The invention features a method of stabilizing free 1-ascorbic acid from oxidation by dispersing the free 1-ascorbic acid in a mixed glycol carrier and a solution containing the ascorbic acid in the mixed glycol solution. The mixed glycol carrier contains a mixture of at least propylene glycol and butylene glycol, but may contain other glycols such as polyethylene glycol, and stabilizing and solubility assisting agents as well.

This application is a continuation application of Ser. No. 09/329,608filed on Jun. 10, 1999, now U.S. Pat. No. 6,087,393. The contents of allof the aforementioned application(s) are hereby incorporated byreference.

BACKGROUND OF THE INVENTION

For many years, researchers have been investigating methods forstabilizing 1-ascorbic acid (vitamin C), due to its beneficialproperties. Indeed, 1-ascorbic acid has many known biological functions,such as the stimulation of collagen synthesis, the strengthening of skintissue against external attack (UV radiation, pollution),depigmentation, activity against free radicals and the compensation forvitamin E deficiency. Some of these beneficial properties have beenreported by England and Seifter in the article “The biochemicalfunctions of ascorbic acid” (Ann. Rev. Nutri. (1986) 6:365-406).

However, due to its alpha-keto lactone structure, ascorbic acid is verysensitive to the influence of environmental parameters such as light,oxygen, and water. An unavoidable degradation of ascorbic acid insolution occurs over time due to its pH and the presence of tracemetals.

This problem has been addressed in a variety of ways in the art. Inorder to reduce or delay the degradation of ascorbic acid in solution,U.S. Pat. No. 5,140,043 recommends stabilization by introducing ascorbicacid into aqueous-alcoholic solutions, formed of at least 80% water andhaving a pH below 3.5. These solutions are not usable in the cosmeticand/or pharmaceutical field because of a combination of pH, drying ofthe skin by the alcohol, and a lack of aesthetic “feel.” Indeed,repeated application of these solutions may disrupt the equilibrium ofthe skin and may in particular irritate, or even burn, the skin.

Others have tried different ways to produce a stable ascorbic acidsolution. B. R. Hajratwala, in “Stability of ascorbic acid”, publishedin the Revue Sciences Pharmaceutiques on Mar. 15, 1905, discloses thatascorbic acid may be stabilized as an acidic aqueous solution by addingan oxyethylenated sorbitan ester surface-active agent. In particular,Hajratwala states that at pH3.4 and 25° C., the addition of this agentreduced the rate of oxidation, and thus the rate of degradation, ofascorbic acid in solution. Hajratwala also discloses the use of achelating agent such as ethylenediaminetetraacetic acid (EDTA) andpackaging under nitrogen, in the absence of light, in order to enhancethe stability of the aqueous ascorbic acid solution. However, such anacidic aqueous solution, applied to the skin, has the same drawbacks asthose described above for acidic aqueous-alcoholic solutions.Furthermore, the stabilization obtained is still insufficient. Otherways of stabilizing ascorbic acid have been proposed, in particular by acoating technique (FR-A- 1,600,826) or by granulation of ascorbic acid(JP-A-53-127,819) for the agri-foods industry.

These techniques, while providing some stability, are, on the one hand,expensive and may, on the other hand, damage the ascorbic acid, forexample during heating. Generally, these techniques lead to compositionsof poor cosmetic acceptability, as in the case of granules.Consequently, none of the previous proposals have made it possible toovercome the technical problem associated with the instability ofascorbic acid in solution, in a form which is suitable for the cosmeticand/or dermatological fields and at a cost which is compatible withindustrial requirements.

Accordingly, an object of the invention is to provide a method andformulation containing ascorbic acid that has improved stability.

Another object of the invention is to provide a method and formulationcontaining ascorbic acid that has proper aesthetic qualities for use ina dermatological or cosmetic product.

A further object of the invention is to provide a method and formulationcontaining ascorbic acid that is relatively inexpensive while providingthe desire stability and aesthetic properties.

These and other objects and features of the invention will be apparentfrom the detailed description and the claims.

SUMMARY OF THE INVENTION

The invention pertains, at least in part, to a method of stabilizingfree 1-ascorbic acid from oxidation by dispersing the free 1-ascorbicacid in a mixed glycol carrier. This mixed glycol carrier provides bothhigh levels of solubility and stability at a relatively low price. Themixed glycol carrier contains a mixture of at least propylene glycol andbutylene glycol, but may contain other glycols such as polyethyleneglycol, and stabilizing and solubility assisting agents as well. Theseadditional agents may include diisopropyl adipate, myristyl etherpropionate, polyacrylamide (e.g., Sepigel 305), isodecyl neopentonate,diethylene glycol monoethyl ether (e.g., transcutol), lactil (a mixtureof sodium lactate, sodium pyrrolidone carboxylic acid, urea,niacinamide, inositol, lactic acid, sodium benzoate, and hydrolizedanimal protein sold by Goldschmidt A. G.), or mixtures thereof.

The invention also features a solution containing free 1-ascorbic acidstabilized from oxidation in the mixed glycol carrier. The mixed glycolcarrier contains a mixture of at least propylene glycol and butyleneglycol, but may contain other glycols such as polyethylene glycol, andstabilizing and solubility assisting agents as well. These additionalagents may include diisopropyl adipate, myristyl ether propionate,Sepigel 305, isodecyl neopentonate, transcutol, lactil, or mixturesthereof. The preferred range of the propylene glycol in the mixedcarrier is 25-80% by weight, with the butylene glycol being 5-30% byweight. A mixed glycol solution of this type can provide a stablesolution of 5% or even higher levels of ascorbic acid without oxidativedegradation. The dispersion may also include a cosmetically,dermatalogically or pharmaceutically acceptable carrier.

DETAILED DESCRIPTION OF THE INVENTION

The invention features a method of stabilizing free 1-ascorbic acid fromoxidation by dispersing the free 1-ascorbic acid in a mixed glycolcarrier and a solution containing the ascorbic acid in the mixed glycolsolution. The mixed glycol carrier contains a mixture of at leastpropylene glycol and butylene glycol, but may contain other glycols suchas polyethylene glycol, and stabilizing and solubility assisting agentsas well. These additional agents may include diisopropyl adipate,myristyl ether propionate, polyacrylamide, isodecyl neopentonate,diethylene glycol monoethyl ether, lactil, or mixtures thereof. Thepreferred range of the propylene glycol in the mixed carrier is 25-80%by weight, with the butylene glycol being 5-30% by weight. A mixedglycol solution of this type can provide a stable solution of 5% or evenhigher levels of ascorbic acid without oxidative degradation.

The following, non-limiting examples help in illustrating the invention.

EXEMPLIFICATION OF THE INVENTION EXAMPLE 1

In this example, solutions were made which incorporated 1-ascorbic acid.This study was performed to test the relative feasibility ofincorporating stabilized free 1-ascorbic acid into a solution. Theinitial solution was made according to the formulation given in Table 1.

TABLE 1 Compound Weight of components in grams L-Ascorbic Acid 5.0Propylene Glycol 94.0 Sepigel 305 1.0

The 1-ascorbic acid was obtained from Sigma. The propylene glycol wasobtained from Olin Chemicals. Sepigel 305 consists of polyacrylamide,C₁₃C₁₄ isoparaffin and laureth-7. An overhead mixer was used to combinethe Sepigel and the propylene glycol. The mixture was then heated toapproximately 50° C. and stirred 3 hours to disperse the Sepigel. The1-ascorbic acid was then added and the mixture was stirred for 30minutes. The resulting mixture had a pH of 2.97. However, this solutiondid not provide the stability or aesthetics required for a cosmeticproduct.

EXAMPLE 2

In this experiment, the solution was altered to increase he stabilityand improve the aesthetics of the product. The same procedure referencedabove was used to make these solutions. The formulations of thesesolutions of this example are given in Table 2.

TABLE 2 Weight of components in grams Compound A B C D PolyethyleneGlycol — — 10.0 — Butylene Glycol 44.5 40 40.0 46.0 Propylene Glycol44.5 35 30.0 35.0 Diisopropyl Adipate (Ceraphyl-230) 5.0 10 10.0 10.0Myristyl Ether Propionate — 5.0 — — Sepigel 305 1.0 1.0 1.0 1.0l-ascorbic acid 5.0 5.0 5.0 5.0

Each solution was made by initially mixing Sepigel 305 with thepropylene glycol at 55-60° C. until the solution became clear. Theremaining compounds were subsequently added and each solution was thenstirred. After prolonged stirring, the resulting solution was uniformlyhazy, except for ‘A.’ ‘A’ was clear with a good viscosity. After addingthe butylene glycol (specifically 1,3 butylene glycol, a material oftenused in cosmetics)and PEG-200, however, the viscosity of the eachsolution decreased. After adding all the ingredients, ‘D’ solution wasdetermined to be superior aesthetically. The non-glycol components areprimarily stabilizing elements and can be replaced with similar polymercomponents.

EXAMPLE 3

In order to improve the ‘feel’ and clarity of the solution, theformulations outlined in Table 3 were attempted. The solutions were madein the same method as outlined in Example 2.

TABLE 3 Weight of components in grams Compound A B C Butylene Glycol 3520 10 Propylene Glycol 39 44 60 Diisopropyl Adipate (Ceraphyl-230) 20 2015 Sepigel 305 1.0 1.0 1.0 l-ascorbic acid 5.0 5.0 5.0

The propylene glycol was heated to 55-60° C. and the Sepigel 305 wassubsequently added. The solution was then stirred by an overhead mixeruntil it was clear. The remaining components of the solutions were thenadded and stirred without additional heating. All of the resultingsolutions were hazy. To ‘A,’ 1.5% Polysorbate 80 was addedunsuccessfully to improve the clarity of the solutions. ‘C’ was theleast hazy.

EXAMPLE 4

In order improve the clarity, the solutions of the formulations outlinedin Table 4 were made. The propylene glycol solution was a 1% solution ofSepigel 305 in propylene glycol.

TABLE 4 Weight of components in grams Compound A B C D E PropyleneGlycol Solution 75 85 80 70 80 Butylene Glycol — — 10 10 DiisopropylAdipate (Ceraphyl-230) 20 — 10 10 Myristyl Ether Propionate (PPG-2) — 10— Isodecyl Neopentonate (DUB ICI) — — — 10 l-ascorbic acid 5 5 5 5 5

The solutions were made by adding the remaining components to thepropylene glycol solution. All of the resulting solutions were somewhathazy. In mixtures ‘B’ and ‘E,’ the ester components separated out fromthe other components of the solution. When heated to 50° C., thesolutions remained the same. Mixture ‘D’ had the lightest “feel.” It isclear that the combination of propylene glycol and butylene glycolprovides advantageous results compared to the solutions lacking thebutylene glycol.

EXAMPLE 5

In the following experiment, transcutol (diethylene glycolmonoethylether) was incorporated into the solution mixture. The propylene glycolsolution was the same as in Example 4. The formulations of the solutionsare outlined in Table 5.

TABLE 5 Weight of components in grams Compound A B Propylene GlycolSolution 65 60 Butylene Glycol 10 10 Diisopropyl Adipate (Ceraphyl-230)15 10 transcutol — 10 l-ascorbic acid 5.0 5.0

The propylene glycol solution was mixed with the remaining ingredients,as discussed in the preceding Examples. As solution ‘A’ cooled to roomtemperature, it became cloudy. When it was reheated, the mixture becameclear. Solution ‘B’ remained clear throughout cooling and reheating.Accordingly, the addition of transcutol appears to provide someadvantage.

EXAMPLE 6

In the following example, the percentage of Sepigel 305 in the propyleneglycol solution was increased to 1.25% to improve the clarity of thesolutions. The procedure was identical to the one outlined in thepreceding Example. The formulations of the solutions are given in Table6.

TABLE 6 Weight of components in grams Compound A B C Propylene GlycolSolution 65 60 50 1,3 Butylene Glycol 15 10 20 Diisopropyl Adipate(Ceraphyl-230) 10 10 15 l-ascorbic acid 5 5 5 transcutol 5 10 5

After mixing the remaining components with the propylene glycolsolution, ‘A’ and ‘C’ were slightly hazy and ‘B’ was clear.Aesthetically, ‘C’ had a “light” feel. Both ‘A’ and ‘B’ were shiny andlight.

EXAMPLE 7

In this example, additional components were added to the solutions. Theformulation of the solutions is outlined in Table 7. The propyleneglycol solution contained 1.25% Sepigel 305.

TABLE 7 Weight of components in grams Compound A B C D Propylene GlycolSolution 70 70 60 60 1,3 Butylene Glycol 10 10 15 15 Diisopropyl Adipate(Ceraphyl-230) 10 10 15 15 DC 344 — 5 — — Lactil 5 — — — l-ascorbic acid5.0 5.0 10 5.0

The 1-ascorbic acid was placed in the propylene glycol solution andheated to approximately 50° C. The mixture was then stirred for about 10minutes, or until the acid dissolved. The remaining components were thenadded. ‘A’ became hazy after adding lactil. The addition of Span 80(Sorbitan monooleate) did not clear the solution. ‘B’ became hazy afterthe addition of DC 344 (Cyclomethicone). The addition of Span 80 did notclarify solution B either. ‘C’ and ‘D’ were clear at elevatedtemperatures, but they became cloudy once they reached room temperature.

EXAMPLE 8

In this example, the pH of the solutions was increased by addingtriethanolamine, magnesium ascorbyl phosphate, and morpholine. Theformulations of the solutions are given in the table below. Thepropylene glycol solution contain 1.25% Sepigel 305.

TABLE 8 Weight of components in grams Compound A B Propylene GlycolSolution 75 65 Butylene Glycol 10 15 Diisopropyl Adipate (Ceraphyl-230)10 10 transcutol — 5 l-ascorbic acid 5.0 5.0

L-ascorbic acid was added to the propylene glycol solution and stirredfor fifteen minutes. The remaining components were then added. The pH ofboth solutions was initially 3.01. After the addition of 1 mltriethanolamine, both solutions became hazy. When morpholine was addedto another sample, both solutions became hazy. Both sodium hydroxide andmagnesium ascorbyl phosphate were not soluble in the solutions.

At room temperature, both ‘A’ and ‘B’ remained clear for seven months.At 40° C., both ‘A’ and ‘B’ started to yellow after about four months.At 50° C., both samples turned yellow after less than a month.

To yet another sample of ‘A,’ an additional 5% of 1-ascorbic acid wasadded. After being warmed slightly and stirred for fifteen minutes, thesolution became clear. The pH of the solution was 2.86. At 50° C., 40°C., and room temperature, ‘A’ was clear. When chilled in therefrigerator, ‘A’ became hazy. After one month at room temperature, thesamples were slightly yellowish. At 50° C. after one month, ‘A’ was verydiscolored.

To a sample of ‘B,’ an additional 5% of 1-ascorbic acid was added at 50°C. The solution remained clear at 50° C., 40° C., and at roomtemperature. When chilled, ‘B’ became cloudy. After one month at roomtemperature, the samples were slightly yellowish. At 50° C. after onemonth, ‘B’ was very discolored.

Equivalents

Those skilled in the art will recognize, or be able to ascertain usingno more than routine experimentation, numerous equivalents to thespecific procedures described herein. Such equivalents are considered tobe within the scope of this invention and are covered by the followingclaims. The contents of all references, issued patents, and publishedpatent applications cited throughout this application are herebyincorporated by reference.

What is claimed is:
 1. A solution for topical use comprising 1-ascorbicacid in a mixed glycol carrier containing propylene glycol and butyleneglycol and wherein said mixed glycol carrier contains substantially nofree water.
 2. The solution of claim 1 where said mixed glycol carriercomprises 25-80% by weight propylene glycol and 5-30% by weight.
 3. Thesolution of claim 1 wherein said mixed glycol carrier further comprisespolyethylene glycol.
 4. The solution of claim 1, further comprising acosmetically, dermatologically, or pharmaceutically acceptable carrier.5. A method of stabilizing free 1-ascorbic acid from oxidation bydispersing said free 1-ascorbic acid in a mixed glycol carrier comprisedof propylene glycol and butylene glycol and wherein said mixed glycolcarrier contains substantially no free water.
 6. The method of claim 1wherein said mixed glycol carrier comprises 25-80% by weight propyleneand 5-30% by weight butylene glycol.
 7. The method of claim 1, whereinthe dispersion is comprised of about 2% to about 15% free 1-ascorbicacid by weight.
 8. The method of claim 1, wherein said mixed glycolcarrier further comprises polyethylene glycol.
 9. The method of claim 1,wherein said mixed glycol carrier further comprises a cosmetically,dermatalogically or pharmaceutically acceptable carrier.